You are here: start » group_2_presentation_2_-_juvenile_idiopathic_arthritis

Differences

This shows you the differences between two versions of the page.

--- group_2_presentation_2_-_juvenile_idiopathic_arthritis [2017/03/09 13:18]
ahsencb
+++ group_2_presentation_2_-_juvenile_idiopathic_arthritis [2018/01/25 15:18] (current)
@@ Line 1: / Line 1: @@
 ======Juvenile Idiopathic Arthritis======
+{{:juvenile_arthritis_powerpoint.pptx|}}
 =====Introduction=====
 Juvenile idiopathic arthritis (JIA), also known as juvenile rheumatoid arthritis (JRA) is a chronic form of arthritis that can be seen in children between the ages of 1-16 (Shiel, n.a). This disease refers to a group of conditions that pertain to joint inflammation (Figure 1). According to The Genetics Home Reference, “It is classified as an autoimmune disorder which means that the immune system malfunctions and attacks the body’s organs and tissues, in this case joints.” Through much research, it has been determined that there are seven types of JIA which are classified in accordance to their signs and symptoms, number of affected joints, results from medical tests and familial history. All seven types of JIA are chronic, thus individuals must develop coping methods that are long lasting and effective. The prevalence of the seven types of JIA are shown in Figure 2  (Genetics Home Reference, 2015).
-==== Systemic Juvenile Idiopathic Arthritis ====
+{{:figure_one_jia.jpg}}
+**Figure 1:** This image illustrates a comparison between a normal joint, osteoarthritis and rheumatoid arthritis. Retrieved from: http://www.onhealth.com/content/1/rheumatoid_arthritis_ra
+=== Systemic Juvenile Idiopathic Arthritis ===
 Systemic juvenile idiopathic arthritis causes inflammation in one or more joints, and its symptoms include high daily fevers that can last up to two weeks either preceding or accompanying the arthritis. A skin rash or enlargement of lymph nodes, liver or spleen are symptoms that differentiate this type of juvenile arthritis from other types (Genetics Home Reference, 2015).
-{{:stages-of-alzheimers.jpg|}}
+=== Oligoarticular Juvenile Idiopathic Arthritis ===
-**Figure 1:** The stages of Alzheimer's disease starting from mild cognitive impairment leading up to more severe stages.
+Oligoarticular juvenile idiopathic arthritis refers primarily to the inflammation of joints. This form of arthritis is prevalent in four or fewer joints in the first six months from when the disease was diagnosed. Depending on the onset of the condition, this form of arthritis can be divided into two subtypes. If the arthritis has not spread to more than four joints after six months, it is considered to be persistent oligoarthritis. If more than four joints are affected, it is classified as extended oligoarthritis (Genetics Home Reference, 2015).
-==== Prognosis ====
+=== Rheumatoid Factor Positive Polyarticular Juvenile Idiopathic Arthritis ===
-Before severe brain degeneration due to Alzheimer’s, it is crucial to diagnose this condition as early as possible. The disease can occur in patients as early as the age of forty (Mayeux & Sano, 1999). Usually these patients have inherited a mutant gene from their parents causing the dieses to show up earlier than usual (Mayeux & Sano, 1999). This is also known as the “early onset” (Mayeux & Sano, 1999).  More commonly Alzheimer’s this dieses attacks individuals around there sixties (Mayeux & Sano, 1999). This form of Alzheimer’s is called the “Late onset”. Studies show that over 90% of individuals are effected around this age (Mayeux & Sano, 1999). However the Late set-onset of Alzheimer’s disease is not completely understood as of yet. Studies show that a mix of environmental, genetic, and life style factors may play a role (Mayeux & Sano, 1999). Both the early set and late set have similar patterns of damage showing up in the brain. Moreover the increasing of one’s age shows a correlation with attaining the dieses (Mayeux & Sano, 1999). Though this is the case the symptoms and signs of Alzheimer’s and dementia are not part of normal aging.
-==== Epidemiology ====
+When inflammation is present in five or more joints within the first six months of the disease, it is considered rheumatoid factor positive polyarticular JIA. Patients with this condition have a positive blood test for proteins called rheumatoid factors. A rheumatoid factor is the amount of protein found in the blood that may attack healthy tissues in the human body. This type of JIA displays symptoms similar to the predominant types of arthritis in adults (Genetics Home Reference, 2015).
-Globally there is an estimated 24 million people with Alzheimer’s disease with 4.6 million cases rising every year (Reitz, Brayne & Mayeux, 2011). This number is predicted to double every 20 years. More over as the population of North America is aging, thus the number of patients with the disorder are increasing particularly in the elderly community (Reitz et al., 2011). The highest prevalence of Alzheimer’s is shown in North America, Western Europe, Latin America and China (Reitz et al., 2011).The age at which people are affected by the disorder ranges around the age of 60 (Reitz et al., 2011). The annual incident rates (per 1000) in these countries are 10.5 in North America, 8.8 in Western Europe, 9.2 in Latin America and 8.0 in China (Reitz et al., 2011). Moreover the prevalence rates of Alzheimer’s disease rise exponentially with age (Reitz et al., 2011). Compared to Europe china and Latin America the prevalence of Alzheimer’s is mainly in the United States (Reitz et al., 2011). The prevalence seems to be higher in the Latin American and African American communities. But the rates are much lower for African communities in their homeland. The reason for this still remains unsure. By the year 2020 World health
+=== Rheumatoid Factor Negative Polyarticular Juvenile Idiopathic Arthritis ===
-Organization’s predict the number of Alzheimer’s patients to reach 29 million (Reitz et al., 2011).
+This type of arthritis is similar to the rheumatoid factor positive polyarticular JIA as it also affects five or more joints. As evident in its name, it tests negative for the rheumatoid factor in the blood (Genetics Home Reference, 2015).
-Risk factors such as family history and genetic factors can play a huge role in developing Alzheimer’s disease. Individuals with Parents, brothers or sisters with the disease are more likely to develop the disorder.  There is an increase in the risk of attaining the illness if more than one family member has the disease. Furthermore scientist have discovered risk genes that increase the likelihood of someone developing the disease. The gene with the strongest risk factor is called the apolipoprotein E-e4 (APOE-e4) which is a factor that increases the chances of Alzheimer’s by 20-25 % (Reitz et al., 2011). If you inherit one APOE-e4 gene from a parent you will have an increased risk, but if you inherit from both parents have an even higher risk (Reitz et al., 2011). By inheriting the gene from both parents the signs and symptoms of Alzheimer’s is going to show up at a younger age than usual (Reitz et al., 2011). Moreover genes that guarantee the disorder are called deterministic genes (Reitz et al., 2011). By coding three proteins, scientists have discovered the genes the variations that directly cause Alzheimer’s disease (Reitz et al., 2011). The three proteins are amyloid precursor protein (APP), presenilin-1 (PS-1) and presenilin-2(PS-2) (Reitz et al., 2011). When these genes cause the Alzheimer’s disorder, it is called “autosomal dominant Alzheimer’s disease (ADAD) or Familial Alzheimer’s disease (Reitz et al., 2011). When effected by this autosomal disease the symptoms usually appear well before the age of 60. It may occur as early as a person’s 30s or 40s. This form of Alzheimer’s have been found in only a few hundred families worldwide (Reitz et al., 2011). This rare form of Alzheimer’s accounts for less than 5% of cases worldwide (Reitz et al., 2011).
-{{:ad_epidimeology.jpeg|}}
+=== Psoriatic Juvenile Idiopathic Arthritis ===
-**Figure 2:** This graph depicts the prevalence of the disease as being most abundant in Brazil, Europe, USA and China.
+Psoriatic juvenile idiopathic arthritis is usually detected in combination with a skin disorder called ‘psoriasis’. This condition is understood by the red patches and irritated skin that are covered by flaky, white scales. Depending on the individual, some are affected by this skin disease prior to developing arthritis, and others notice the the skin condition while first developing arthritis. Other symptoms of this type of arthritis include abnormalities of the fingers and nails like uneven lengths and deformed fingers or vision problems (Genetics Home Reference, 2015).
-======Pathophysiology======
+=== Enthesitis-related Juvenile Idiopathic Arthritis ====
-==== Neuropathology ====
+Enthesitis-related juvenile idiopathic arthritis is classified by tenderness where the bone meets the tendon, ligament, or other connective tissue. This is usually accompanied by inflammation in joints and other related areas (Genetics Home Reference, 2015).
-The hallmarks of Alzheimer’s disease involve a loss of neurons, the shrinkage of large cortical neurons and synapses in the brain over a period of time. The result is an eventual degeneration in the cingulate gyrus, temporal and parietal lobes, the frontal cortex, brainstem nuclei and locus coruleus. In addition, the disease is characterized amyloid plaques and neurofibrillary tangles concentrated in vulnerable areas in the brain and are visible under a microscope. The plaques are made up fibrous proteins known as β-amyloid, diffuse plaques (poorly defined amyloids) and burnt-out plaques containing an isolated amyloid core. These plaques form clumps in the cortex and are hypothesized to result in a cascade of events leading to cell dysfunction and necrosis. (Yaari, 2007) Even with increasing evidence to suggest  this, it is not a view supported by all. (Hardy, 1991). Neurofibrillary tangles are associated with tau, a microtubule protein that has become hyperphosphorylated and clustered together with others of its kind. Though these plaques and tangles are not only seen Alzheimer’s sufferers, those who do suffer from the disease exhibit a much larger prevalence of them than one who does not suffer from it. (Bouras, 1994).
+=== Undifferentiated Arthritis===
-In Alzheimer’s disease, polymerization and misfolding of generally soluble proteins occurs as a result of the accumulation of the plaques inside cells as discussed above. (Selkoe, 2004) The plaques are composed of the peptides β-amyloid (part of the amyloid precursor protein), sized 39-43 amino acids long. The precursor protein’s cell function in the brain is associated with the growth and survival of neurons.  (Yaari, 2007)
+Undifferentiated arthritis is given to patients who have symptoms that are not explained by the descriptions of any of the above forms of JIA or who have fit the criteria for more than one of the given descriptions of JIA (Genetics Home Reference, 2015).
-When phosphorylated, the protein tau stabilizes microtubules. In Alzheimer’s sufferers hyperphosphorylation occurs in the tau proteins, making it aggregate much more easily to form neurofibrillary tangles. This essentially disengages the transport system of the neurons. (Hernandez, 2007)
-{{ :alzheimer_brain.jpg }}
+ {{:jia_image_2.png}}
-**Figure 3:**This figure shows a comparison of a normal brain and one with Alzheimer's disease. The atrophy and degeneration of brain tissue in the brain on the right is visible. (Alz, 2011).
+**Figure 2:** This graph shows the percentage at which each subtype of JIA is prevalent. Retrieved from: https://warmsocks.files.wordpress.com/2012/08/jiabreakdown.png
-====== Disease Mechanism ======
+=====Symptoms and Diagnosis=====
-The biochemistry or course of actions that results in Alzheimer’s disease is not yet definite. Many hypotheses have been established over the years in order to explain the phenomenon. Of all of the existing theories, three have gained ample recognition and support in comparison to the rest. Before examining the theories below, it is important to note that there is no causational link clearly identified in the literature. The three most popular hypotheses include: Amyloid Hypothesis, Cholinergic hypothesis and Tau hypothesis.
+JIA is diagnosed once symptoms are persistent for at least six weeks since the diagnosis (Shiel, n.a). Common symptoms of JIA include swelling, redness, and warmth of joints. Researchers and scientists have attempted to formulate a criteria for the precise diagnosis of JIA (Nelson & Kilegman, 2016). The proposed criteria includes six requirements. Firstly, polyarticular or monoarticular arthritis must be present for at least six weeks or in the presence of Iritis, rash, flexion contractures, ankyloses, muscle wasting, anemia, white blood cell count of 20000, and/or cervical spine pain. The criteria of symptoms for polyarticular or monoarticular arthritis present for 6 weeks or less includes no migraines for at least 1 week, no symptomatic response to therapeutic blood levels of salicylate (20 mg/100 ml or above), preponderance of small joint involvement, involvement of the temporomandibular joints, and/or morning stiffness. Next, polyarticular or monoarticular arthritis present for 6 weeks or less is accompanied by pericarditis in the absence of endocarditis. Fourthly, the criteria includes constitutional symptoms, which are known as any combination of fever, weakness, or weight loss . The fifth criteria mentions the presence of elevated erythrocyte sedimentation rate. Lastly the exclusion of all other diagnoses such as rheumatic fever, systemic lupus erythematosus, periarteritis nodosa, dermatomyositis, scleroderma, tuberculosis synovitis, leukemia, lymphoma, septic arthritis, osteomyelitis, sickle cell anemia and serum sickness. This criterion was put together to ensure that the diagnosis of JIA was accurate (Grossman & Mukhopadhyay, 1975).
-==== Amyloid Hypothesis ====
+===Flares===
-The foundation of this theory rests upon the idea that aggregated β-amyloid fibers lead to cytotoxicity within cells and in turn disrupt calcium ion homeostasis, leading to apoptosis. This apoptosis leads to the death of brain matter as seen in the brains of Alzheimer’s sufferers. (Yanker, 1990) Several mutations have been linked to early onset familial Alzheimer’s disease in three genes: PSEN1, PSEN2, and amyloid precursor protein APP. Such mutations would cause aggregate stress and disrupt the normal function of β-amyloid peptide, leading to aggregation. (Karran, 2011) In a study conducted by Lijima et. Al (2004), mouse models showed support for the theory as they demonstrated that β-amyloid aggregates caused them cognitive impairment. Another reason this theory has gained popularity is due to chromosomal effects. the APP gene is located on chromosome 21, and those with trisomy 21 (down syndrome) exhibit similar late cognitive effects as those with Alzheimer’s. (Nistor, 2007)
+Flares are known as a classification of symptoms referring to joint pain and inflammation, which are more prevalent in areas of the body highlighted in figure 3. Flares can last from time periods ranging from weeks to months. JIA patients tend to have periods of remission where these symptoms aren’t as prevalent as they would have been in the past. Following this grace period where pain is minimal, these symptoms can reappear, and this is known as a relapse. This notion of relapsing and remission varies from patient to patient and can also be a known trend with other symptoms as well (Shiel, n.a).
-{{ :screen_shot_2016-03-25_at_6.36.45_pm.png }}
+{{:fig_3_jia.jpg}}
-**Figure 4:**This figure shows a simplification of the cascade of events that occur in Alzheimer's disease as predicted by the Amyloid Hypothesis. (Karran, 2011).
+**Figure 3:** This shows the location of different body parts with high prevalence of body inflammation Retrieved from: http://www.onhealth.com/content/1/rheumatoid_arthritis_ra
+===Fever====
-==== Cholinergic Hypothesis ====
+A fever is a common symptom for JIA and can be classified according to various degrees of a spectrum. A fever in an individual who may have JIA can be recognized in three different states. “Intermittent fever with a daily single high spike of temperature to 104-105 fahrenheit , then returning down to a normal temperature. A remittent fever with a persistent elevation of 100-101 fahrenheit with occasional, somewhat irregular increases in temperature to 103-104  fahrenheit. Lastly, low grade fever with periodic elevation of temperature to 100-101 fahrenheit, the elevations frequently occurring in the late afternoon or evening, the morning temperature being normal (Grossman & Mukhopadhyay, 1975).”
-One of the older theories, the cholinergic hypothesis states that Alzheimer’s associated brain tissue degradation is a result of the deficiency in the neurotransmitter acetylcholine. Research now shows that there isn’t a causational relationship acetylcholine levels and the onset of Alzheimer’s disease. It is shown, however, that lower levels of acetylcholine are present in patients with the disease and this may be due to brain tissue damage. In the recent past, the neurotransmitter has been proposed to be a potential causal agent in the formation of aggregates and neuroinflammation. (Shen, 2004)
+===Morning Stiffness===
-==== Tau Hypothesis ====
+Morning stiffness is a symptom that helps with the diagnosis of JIA. It is describes as the difficulty in moving muscles after a period of rest or inactivity. Individuals feel this pain in the morning after waking up, and it is not a result of pain. With increased activity and movement throughout the day, muscles become less stiff. Muscle stiffness can last between several minutes to several hours. The degree to which morning stiffness occurs can also vary. It can be  severe to the extent that the child cannot move without help from another person. In these circumstances, the combination of a warm bath and an increase in activity will aid with the relief of the stiffness. Other times in the day where morning stiffness is prevalent is after a nap or sitting down for a prolonged period, however, this is usually not as sever as the morning occurrence.  Morning stiffness is an important differential characteristic between the symptoms of JIA/rheumatic fever and septic arthritis (Miller, 1994).
-The Tau Hypothesis suggests that the formation of Neurofibrillary tangles (NFTs) --that is characteristic of Alzheimer’s Disease-- is due to the hyperphosphorylation of Tau proteins. Tau proteins normally play a role of structural support as they are responsible for microtubule stabilization. However, Tau Hyphosphorylation results in clumping of other Tau proteins which eventually develop into NFTs in Alzheimer’s Disease. Research has shown that Tau Hyperphosphorylation has led to neuronal cell death through microtubule dysfunction which disrupts the structural integrity of the cell. As a result, this has been associated with the cognitive decline that is seen in Alzheimer’s Disease (Maccioni et al., 2010).
-====== Intervention Strategies ======
+===Rheumatoid Rash====
-==== Treatment ====
+This symptom is extremely helpful when diagnosing JIA, especially in the acute onset of disease. According to Miller, “the characteristic rheumatoid rash is an erythematous, salmon-pink, evanescent, usually circumscribed macular (although occasionally maculopapular) eruption involving the trunk, neck, velar aspect to the arms, inner aspect of the thighs, buttocks and face. It may last for only a few minutes, a few hours or several years.” Again, the degree to which the rash may last varies between a few minutes to many hours. It appears strongly during times of high fever or during warm baths. Many times, the rash experienced in patients who have JIA can be mistaken for erythema annulare or marginatum, however erythema annulare or marginatum do not spread to facial regions (Miller, 1994).
-The treatment of Alzheimer’s disease primarily involves the use of pharmacological measures to alleviate the adverse symptoms that patients experience. One prominent pharmacological treatment is the administration of Cholinesterase inhibitors. The use of these drugs has shown great promise in clinical trials with respect to the treatment of AD physical symptoms and it has shown to even improve cognitive performance in individuals with AD. These drugs inhibit the enzyme, Acetylcholinesterase in the neuronal synapse which leads to a greater concentration and increased temporal activation of the neurotransmitter, Acetylcholinesterase. There are four commonly used drugs that act as Cholinesterase inhibitors and they are Tacrine, Donepezil, Rivastigmine, and Galantamine, respectively (Grossberg & Desai, 2003). Other pharmacological drugs include the administration of antioxidants such as Alpha tocopherol and selegiline. These compounds function by inhibiting an enzyme that is involved in oxidative stress in neuronal cells. Antioxidants have also shown to be promising in the treatment of AD as there have been clinical trials that demonstrated a slower rate of AD development in groups that were given selegiline (Ibbotson & Goa, 2002).
-Even though antioxidants and Cholinesterase inhibitors are effective in treating AD symptoms, they are not effective in altering the overall pathogenesis of AD. For these reasons, novel treatments are been developed—especially by targeting Amyloid-β plaques through the form of Amyloid-β immunotherapy. This unique form of treatment utilizes the immune system to stop the accumulation of Amyloid-β plaques. Amyloid-β immunotherapy is divided into two different types which are active and passive immunotherapy, respectively. See **Figure** below for details. Active immunization is further divided into two types. The first type involves the injection of the 42 amino acid Aβ peptide which subsequently results in Antigen Presenting Cell (APC) recognition and phagocytosis of these peptides. The APCs then present the processed Aβ peptide to T cells which leads to the proliferation of B cells that produce anti-Aβ plaque antibodies that are specific for the Aβ peptide. The second active immunization type uses almost the same principle as the first type but differs in the initial administration. Instead of direct administration of the Aβ peptide, small fragments of the Aβ peptide are attached to a carrier protein and the carrier protein is the antigen that is recognized by APCs. On the other hand, passive immunization involves direct administration of anti-Aβ plaque antibodies and this would be useful for individuals who are unable to generate an immune response to the Aβ plaques. It is important to note that Aβ immunotherapy has shown promising results in mice models but further research needs to be conduced in humans for effective AD treatment (Schenk, 2002). Please see Figure 4 for details.
+{{:fig_4_jia.jpg?300}}
-{{ :snip20160327_1.png }}
+**Figure 4:** This image is showing the rheumatoid rash when present on a child’s face.  Retrieved from: http://www.findarthritistreatment.com/wp-content/uploads/2013/12/Skin-rash.jpg
-**Figure 5**: This figure shows two promising approaches of utilizing anti-Aβ plaque antibodies to limit the progression of Alzheimer's Disease (Schenk, 2002).
+===Subcutaneous Nodules===
-==== Management ====
+Nodules have been observed in approximately 10% of children who have been diagnosed with JIA and can appear subcutaneously, as shown in figure 5. Characteristics of nodules include variances in sizes (from a few millimeters to several centimetres in diameter), nontender texture, no attachment to overlying skin and therefore moving freely under the skin . Many times, they are found over the extensor tendon sheath of the hands, specifically over the metacarpophalangeal, proximal interphalangeal and distal interphalangeal joints . They are also found near the olecranon process of the elbow, over the anterior tibial surfaces and around the wrists and when fever is prevalent in the patient, nodules are found along the tendons of the erector spinae group and over the aponeurosis of the scalp (Miller, 1994).
-The management of Alzheimer’s disease involves the contributions of a variety of health care professionals to control the severity of the patient’s symptoms. To begin, physicians are crucial in the management of AD as they are the primary means to recommend pharmacological treatments for treating symptoms. Physicians treat various physical symptoms that are associated with AD such as insomnia and aggression. Clinical psychologists are also crucial for the treatment of behavioral aspects of the disease such as depression and anxiety. Lastly, social workers are responsible for providing emotional and physical support to the patient and the family members (Grossberg & Desai, 2003).
-Alzheimer’s disease can also be managed through therapeutic measures, particularly non-pharmacological means. One type includes psychosocial management which includes educating the patient’s caregivers to reduce the distress of both the caregivers and the patient. Caregivers can also be trained in a management technique called Interpersonal management which involves attending to patient’s unmet needs such as pain, hunger and thirst. Finally, environmental management techniques are important for treating AD patients who suffer from neurological symptoms as a result of changing environmental stimulations. Specifically, a condition that AD patients frequently experience is termed the sundowning phenomenon, which is when patients experience greater distress and neurological symptoms during daytime periods of high sun time. To reduce these symptoms, it is advised to make patients feel comfortable through various relaxation techniques (Gauthier et al., 2010).
+{{:fig_5_jia.jpg?300}}
-==== Prevention ====
+**Figure 5:** This image illustrates what nodules look like on the hands of a child. Retrieved from: http://c.ymcdn.com/sites/www.aocd.org/resource/resmgr/ddb/rheumatoid_nodules_1_low.jpg
-Although Alzheimer's Disease (AD) has a number of non-modifiable genetic risk factors, there are also potentially modifiable risk factors such as hypertension, hyperlipidemia and environmental exposures that can be improved with improved with proper care and preventative measures (Patterson et al., 2008). Beginning with genetic factors, there are three gene mutations that almost always result in the occurrence of Alzheimer's Disease. These include a mutation in either the amyloid precursor protein gene, presenilin-1 gene or presenilin-2 gene (Patterson et al., 2008). In terms of non-genetic factors, studies have shown a correlation between systolic blood pressure and an increased risk of dementia. After the study group with high systolic blood pressure received antihypertensive treatment, the incidence of dementia was reduced by 50% from 7.7 to 3.8 cases per 1000 patients in the treatment group (Patterson et al., 2008).
-A second non-genetic risk factor for Alzheimer's is the increased risk of the disease with hyperlipidemia. Speculative studies have suggested that increased levels of total serum cholesterol levels have been linked to increased risk of Alzheimer's (Patterson et al., 2008). However, there are many studies that have downplayed the role of increased cholesterol in Alzheimer's patients. For instance, there is no correlation between cholesterol and beta-amyloid peptide production (Ledesma et al., 2005).
-Despite the many factors leading the Alzheimer's, the consumption of several medications have been known to reduce the risk of the disease. These primarily include non-steroidal anti-inflammatory drugs (NSAIDs) and vitamin supplements (Patterson et al., 2008). Follow-up studies revealed that although the consumption of NSAIDs does not directly reduce the risk of Alzheimer's, patients who took an NSAID such as Naproxen were protected from the onset of AD by 67% compared to the placebo (Imbimbo, 2010). More specifically, it has been hypothesized that the consumption of NSAIDs might only be beneficial in the early stages of AD, during the initial Beta-Amyloid deposition process (Imbimbo, 2010).
-====== Further Research and Future Applications ======
+===Uveitis Eye condition===
-The current issue with the treatments available for Alzheimer's today are due to the fact that only symptomatic treatments exist, which all try to counteract the neurotransmitter imbalance (Yiannopoulou et al., 2013). Still under extensive research are the "disease-modifying drugs" which alter the course of the disease. In order to stop the onset of Alzheimer's, future drugs must be able to disturb the pathogenic steps responsible for the symptoms. Some of these steps include the deposition of Beta-Amyloid plaques, inflammation, oxidative damage and iron deregulation (Yiannopoulou et al., 2013). Current disease-modifying therapies for AD are in phase I-III of their trials. All the future research will be heavily focused on preventing the deposition and misfolding of Beta-Amyloid and tau proteins. Prospective drugs as of right now include tramiprosate, currently in phase III of clinical trials and colostrinin which is currently in phase II (Yiannopoulou, 2013). Tramiprosate aims to interfere with the binding of glycosaminoglycans and beta-amyloid while colostrinin inhibits beta-amyloid aggression and improves cognitive performance in animal models (Yiannopoulou, 2013).
-Another possible strategy under study is immunotherapy. Both active immunization through vaccination and passive immunization through monoclonal antibodies are being studies (Yiannopoulou, 2013). This form of treatment proved to be controversial after a phase II vaccination trial resulted in cases of meningoencephalitis in 6% of the cases.
+Juvenile rheumatoid arthritis can also lead to an eye condition called uveitis, also named iridocyclitis or iritis . This may or may not lead to any symptoms arising, however some symptoms of this condition are red eyes, eye pain, vision changes and sensitivity to light. Uveitis is known as the swelling and irritation of the uvea, which is the middle layer of the eye (Goldstein et al, 2013).
+===Blood Tests for JIA===
+__Rheumatoid factor (RF)__ is a protein that is produced in the blood in some forms of arthritis. This is more common in adults with rheumatoid arthritis, however it is found in 5% of children with JIA (SickKids, 2012). The RF test is a test that is used to detect and measure levels of a specific antibody directed against the blood component immunoglobulin (Arthritis Foundation, 2016).
+__The liver function test (LFT)__ is a test that determines whether or not the liver is healthy and working normally. There are many medications that are used to treat arthritis, such as methotrexate. Medications may play a role in overburdening the liver, therefore doctors may order an LFT to determine the medication that is causing the damage (Arthritis Foundation, 2016).
+__Antinuclear antibody (ANA)__ is a test used to look at autoantibodies in the blood. Autoantibodies are proteins in the immune system, and they are effective indicators used to determine whether children and teenagers with JIA have an increased risk for eye disease (SickKids, 2012).
+__Complete Blood Count (CBC)__ measures three types of cells that are found in the blood: red cells, white blood cells and platelets. This test is useful when discovering more about the condition. For example, kids with low red blood cell counts are usually the ones who are suffering from JIA (Arthritis Foundation, 2016).
+=====Causes and Risk Factors=====
+It has been determined that most cases of JIA are sporadic, meaning that they occur in patients who don’t necessarily have a history of the disorder in their family (Genetics Home Reference, 2015). With that being said, there are many predisposed factors that affect the prevalence of JIA. Infectious agents, immunologic abnormalities of the host, physical trauma to joints, psychological trauma to the child, and allergic reactions to drugs, foods, or toxins can all potentially lead the diagnosis of JIA. With that being said, there is ultimately no clear evidence that proves that these are leadings causes of JIA. JIA is not considered to be a familial disease except in the place in which there is an onset of pauciarticular arthritis. Furthermore, there has been no evidence showing that JIA is transmissible. Various kinds of JIA have been shown to differ in sex, age, types of complications and prognosis, however epidemiologic studies have not been able to clarify these observations (Schaller, 1997). A small percentage of cases of JIA have shown to have run in the family, however the inheritance pattern of the conditions remains unclear (Genetics Home Reference, 2015).
+Maternal smoking has also been observed in the onset of JIA. A mother who smokes while pregnant can induce some permanent immunological abnormality in the child which can later lead to development of arthritis in the child.  Smoking while pregnant may also result in a low birth weight which could in turn lead to an increase in the susceptibility to infection and JIA. Lastly, second-hand smoking leads to a contaminated environment in which the risk of JIA during the early years of that child’s life increases (Symmons, 2005).
+{{:fig_6_jia.jpg?600}}
+**Figure 6:** This image illustrates where rheumatoid arthritis is present on a hand. Retrieved from: https://www.epainassist.com/images/Juvenile-Arthritis.jpg
+=====Epidemiology=====
+The incidence of JIA in North America and Europe  is 4 - 16 affected children out of a sub-population of 10000 children. 1 in 1000, or approximately 294000 children in the United States, are affected by the most common type of JIA in the United States, which is oligoarticular JIA. For reasons that continue to be studied, females seem to be affected with JIA more frequently than males. In the case of enthesitis-related JIA, males are affected more often than females. Furthermore, the incidence of JIA varies between different populations and ethnic groups (Genetics Home Reference, 2015).
+{{:fig_7_jia.png?550}}
+**Figure 7:** This image shows the prevalence of the common forms of arthritis in the United States. Retrieved from: https://rheumatoidarthritis.net/wp-content/uploads/2013/07/prevalence_arthritis.png
+In a study conducted by Saurenmann et al, questionnaires pertaining to ethnicity were distributed to patients with JIA in the Toronto region and then followed up at the Hospital for Sick Children in Toronto. Upon the analysis of the results, the frequency of JIA in European descendants had about 69.7% of their patients diagnosed with JIA, which patients in the Toronto region has about 54.7%. Statistically, lower incidences of JIA were shown in individuals from black, Asian, or Indian subcontinental origins. Kids from the European origin had a higher relative rate for developing any of the subtypes of juvenile arthritis other than oligoarthritis or psoriatic. Patients of the Asian origin showed to have a greater chance of being diagnosed with enthesitis-related JIA while those of black or Native North American origin were more likely to develop polyarticular rheumatoid positive JIA (Saurenmann, 2007).
+===== Pathophysiology =====
+==== Genetic Susceptibility====
+JIA is believed to be a complex genetic trait. A complex genetic trait is defined as phenotypes not exhibiting classic mendelian inheritance patterns and therefore, cannot be attributed to variants in a single gene locus. Thus, JIA is a disease which is believed to be determined by a number of genetic and environmental factors (Glass and Giannini, 1999).
+=== HLA and non-HLA Polymorphisms  ===
+There are two broad categories for genetic susceptibility genes: human leucocyte antigen (HLA) genes and non HLA-related genes. As a polygenic disease, JIA is mostly affected at the HLA region, while the non-HLA loci exhibit moderate or weak genetic influence  on susceptibility (Prahalad and Glass, 2008). JIA is influenced by both HLA class I and HLA class II alleles, which contain certain peptides leading to the activation of certain autoreactive T cells (Wedderburn et al., 2001). Several genetic studies have shown the contribution of polymorphisms in the major histocompatibility complex (MHC). The MHC region is on chromosome 6 and is packed with more than 200 genes, many of which are essential to the immune system. Since MHC class II genes play a great role as a genetic risk factor for JIA, CD4+ T cells play a crucial role in disease development. Associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations (Figure 8) (Prahalad and Glass, 2008).
+{{:jia_fig_8.png|}}
+**Figure 8:**This figure shows several associations between JIA subtypes and different HLA alleles. Retrieved from (Prahalad and Glass, 2008).
+In addition to associations between numerous HLA variants and JIA, non-HLA polymorphisms have also shown to be linked to JIA. For example, genes such as PTPN22, tumor necrosis factor (TNF) alpha (TNFA), MIF, WISP3 and SLC11A6 have been associated with JIA  (Figure 9) (Prahalad, 2004; Rosen et al., 2003).
+{{:jia_fig_9.png?400}}
+**Figure 9:**This figure shows non-HLA genetic genes associated with JIA that have been independently confirmed. Retrieved from (Prahalad and Glass, 2008)
+=== Twin Studies  ===
+Family studies have provided strong evidence for genetic factors contributing to the susceptibility to JIA. For instance, twin and affected sibling pair (ASP) studies have supported the role for genetic susceptibility to JIA. Specifically, they have shown that monozygotic twin concordance rates for JIA vary between 25 to 40%, a stark contrast to the population prevalence of 1 in 1000 of having the disease (Ansell et al., 1969; Baum and Fink, 1968; Savolainen et al., 2000).
+In the largest twin study from the JIA ASP registry conducted by Prahalad and colleagues in 2000, 14 pairs of twins concordant for JIA registered in the National Institute for Arthritis and Musculoskeletal and Skin Diseases were analyzed. Of these 14 pairs of monozygotic twins, 12 were concordant for presence or absence of anti-nuclear antibodies. Prahalad and colleagues found that the first twins to develop JIA did so with an average of 5.5 months before the second twins. This was statistically significant and different compared to the 104 non-twin affected siblings pairs in the registry, who showed a 37 month difference in age at onset between the first and second sibling (Prahalad et al., 2000). Together, these studies solidify evidence for genetic factors in the susceptibility to JIA.
+===Genetic Variables Underlying Autoimmunity ===
+Several studies have shown that clinically distinct autoimmune phenotypes cluster in individuals and families. The data supports the hypothesis that common genetic factors might predispose to clinically distinct autoimmune phenotypes. There are genetic variants which influence susceptibility to multiple clinically distinct autoimmune disorders (Figure 10) (Prahalad and Glass, 2008).
+{{:jia_fig_10.png|}}
+**Figure 10:**This figure shows different examples of genes associated with multiple autoimmune diseases. Retrieved from (Prahalad and Glass, 2008).
+==== Environmental Factors ====
+The cause of JIA is assumed to be multifactorial, as in the case of most human autoimmune diseases. Unlike JIA, a healthy immune system consists of effector and regulatory mechanisms which are kept in balance. Therefore, the innate and adaptive immune systems closely interact. A genetically susceptible individual might develop a deleterious and uncontrolled response towards a self-antigen on exposure to an unknown environmental trigger. In JIA, it can lead to a self-perpetuating loop of activation of both innate and adaptive immunity, causing tissue damage (Prakhen, Albani, Martini, 2011).
+=== Stress and Psychological Factors ===
+The influence of stressful life events and psychological factors before the onset of JIA as a disease trigger has been studied. In a study by Henoch and colleagues which compared 88 children with JIA to 2952 geographically matched controls, results showed that children whose parents were unmarried due to divorce, separation, or death comprised 28.4% of the JIA population, compared to 10.6% in controls (Henoch, Batson, Baum, 1978).
+Stress was also suggested as a contributing factor to the disease. It is a known stimulator to the sympathetic nervous system (SNS) and thus increases the production of interleukin 6, which is one of the most important inflammatory cytokines in JIA (Roupe et al., 2000).
+Although psychological factors and stress may play a role for the onset of JIA, more research needs to be conducted since past studies have had several methodological shortcomings (Berkun, Padeh, 2010).
+=== Smoking ===
+Smoking is the strongest known environmental risk factor for developing rheumatoid arthritis (RA) in adults. The risk of RA from smoking has been showed by the number of shared epitope copies, which suggest gene-environment interaction. Specifically, the strongest known genetic risk factor for RA is a specific sequence of amino acids on HLA-DRB1 allele. In addition, the risk of developing RA from gene-environment interactions increases with the intensity of smoking (Liao et al., 2009).
+All this suggests that smoke is a stimulator of the immune system and that the exposure to tobacco products during fetal life may influence the developing immune system of the fetus. This can lead to an increased susceptibility to infectious agents and thereafter, trigger arthritis as well as subsequent autoimmune diseases. Jaakkola and Gissler conducted a study assessing the relation between maternal smoking in pregnancy and the risk of inflammatory polyarthropathies, in particular JIA in the first years of life. 58 841 newborn Finnish children until the age of 7 were analyzed. Findings showed that there was a 2-fold higher rate of polyarthropathies during the first 7 years of life in children of smoking mothers, compared to non-smoking ones. In addition, the maternal smoking effect was found prevalent to girls, who experienced 6-fold greater likelihood for JIA compared to unexposed boys (Jaakkola and Gissler, 2005).
+=== Infectious agents and JIA  ===
+Infectious agents are believed to be important environmental factors in the development of autoimmunity. An infectious agent may induce a cross-reactive immune response, thereby leading to inflammation provoked by antigen-presenting cells (APCs). This can lead to increased immunogenicity, priming of T cells and subsequent autoimmunity (Berkun and Padeh, 2009). A study by Carlens and colleagues showed that infections during the first year of life and factors related to size and timing of birth were associated with increased risk of developing JIA (Carlens et al., 2009) . However, more research needs to be conducted to understand the role of environmental factors on JIA.
+====Immunology of JIA ====
+The overarching mechanism in all Juvenile Idiopathic Arthritis (JIA) subsets is the activation of the immune system. Different components are involved in each subtype and additional variation may exist within subtypes (Malmström, Catrina & Klareskog, 2016). Over the years, there has been considerable progress in understanding the immune-inflammatory reaction.
+=== Auto-Immunity ===
+Much of the scientific community believe the disease is initiated as a result of molecular mimicry between epitopes on antigens present on infectious agents and autoantigens. Molecular mimicry, by epitope spreading, overcomes tolerance mechanisms and results in autoimmunity. Over the years, two major subtypes of JIA have been identified on the basis of the presence or absence of auto-antigens: antibodies to citrullinated protein antigens (ACPAs) and rheumatoid factor (RF) (Malmström, Catrina & Klareskog, 2016).
+Both subsets have different disease courses. The seropositive form usually means severe pathology. The seronegative forms of arthritis are not well understood and appear to be more heterogeneous compared to the seropositive variant (Malmström, Catrina & Klareskog, 2016).
+===Antibodies to Citrullinated Protein Antigens (ACPA)===
+ACPAs are important for the diagnosis of JIA. These are the patient’s own antibodies which have been modified by citrullination, a process where proteins’ arginine residues are converted to citrulline post-translationally by the enzyme peptidyl arginine deiminase (PAD) (Figure 11). Once modified, the body recognizes its own antigens to be foreign, causing an immune response (Demoruelle & Deane, 2011).
+{{:acap.jpg|}}
+**Figure 11:**This figure shows the process of citrullination. Retrieved from: https://www.hopkinsarthritis.org/wp-content/uploads/2012/08/round4-slide-12.jpg
+===Rheumatoid Factor (RF)===
+RF is an autoantibody derived from IgM that targets the Fc portion of IgG, specifically IgG1 to form immune complexes. These complexes are present in the synovial fluid along with IgG-producing B cells. Additionally, it can form complexes with complement proteins further promoting inflammation. Although RF has been associated with the pathogenesis of RA, it is possible for patients to develop arthritis without it (McInnes & Schett, 2011).
+Interestingly, the literature suggests that RA-associated antibodies are present in the blood several years before joint inflammation signs are present. It is possible that anti-citrullination precedes the onset of joint inflammation which may be triggered in the lungs or other mucosal regions (Malmström, Catrina & Klareskog, 2016).
+===Inflammation===
+JIA is considered a T-cell mediated disease in which CD4+ T cells exacerbate inflammation in rheumatoid joints. Majority of the CD4+ T cells in joints appear to be of the Th1 type, with memory and activation markers. T cells in joints increase in number by recruitment, resistance to apoptosis and accumulation. For this process, cytokines are of importance.
+Cytokines are protein messengers that transmit signals from one cell to another by binding to specific receptors on the surface of cells. Both pro- and anti-inflammatory cytokines, chemokines, and mitogenic factors are produced, but proinflammatory mediators predominate during the active phase of disease.Tumor necrosis factor alpha (TNFα)‎, IL-1, IL-6 and IL-17 are of key importance in the pathogenesis of inflammation in RA. IL-1 and TNFα‎ are also key players in the regulation of mediators of connective tissue damage by synoviocytes, including matrix metalloproteinases (MMPs) and prostaglandins (Figure 12) (Nath Maini, 2010).
+ACPAs may also bind to citrullinated proteins directly in the synovial membrane. Immune complexes between citrullinated proteins ,such as fibrinogen, and ACPA-igG can drive inflammation (including the production of IL-6 and tumor necrosis factor) by engaging both toll-like receptor (TLR4) and Fc receptors (Nath Maini, 2010).
+Furthermore, these cytokines in combination with the cytokines monocyte colony stimulating factor (M-CSF) and receptor activator of NF-κβ‎ ligand (RANKL), activate osteoclasts leading to bone damage. TNFα‎ regulates production of IL-1 and together these two cytokines induce rheumatoid inflammation and damage (Nath Maini, 2010).
+Both ACPA- and RF-dependent events could contribute to the initiation and propagation of chronic synovial inflammation, and further synergize with T cell activation and enhance the local production of autoantibodies (McInnes & Schett, 2011).
+{{:screen_shot_2018-03-09_at_5.59.54_pm.png|}}
+**Figure 12:**This figure shows a summary of the pathogenic pathways in JIA. Retrieved from: https://www.researchgate.net/profile/Abdullah_Nahian/publication/263585727/figure/fig1/AS:202832654409738@1425370481906/Figure-illustrates-the-pathogenic-pathways-of-rheumatoid-arthritis-following-31-38.png
+===Bone Destruction===
+Osteoclasts, cells that line the bone and are responsible for the breakdown of bone tissue, have an important role in ACPA-dependent pathology. ACPAs generated from B cells found in the synovial fluid of patients with RA are able to promote osteoclastogenesis and bone resorption. The effects of these antibodies are mediated both by direct recognition and activation of Fc receptors on osteoclasts. Antibodies can exert a specific function on osteoclasts at the earliest stages of disease development and before joint inflammation appears (McInnes & Schett, 2011).
+The literature suggests that osteoclasts and osteoclast precursors might be the major cell types that express citrullinated antigens on their surface in the normal non-inflamed bone and joint compartment, making precursor cells prime targets for circulating ACPAs. This feature is associated with the role of PADs but the exact role of PADs and citrullination in osteoclast differentiation is unknown (Malmström, Catrina & Klareskog, 2016).
+====== Treatments ======
+It is important to understand that treatment options for individuals with juvenile idiopathic arthritis focus primarily on managing the progression of the disease. While pharmacologic treatments do not cure the disease, specific types of physical therapy, drug therapy and surgical procedures aim to sustain the child’s physical and psychological integrity and minimizing side effects. In effect, a combination of the following types of intervention are most beneficial, however the process of recovery varies with the individual’s risk for disease progression.   (Ravelli & Martini, 2007).
+==== Physical Therapy ====
+===Heat or Cold ===
+Physical treatments are often combined with other forms of treatment to ensure maximal efforts of juvenile idiopathic arthritis management. The application of heat to affected areas is soothing, as it increases blood flow and alleviates muscle or joint stiffness. Applying a cold pack or a compress numbs nerve endings associated with swollen joints, which reduces inflammation and swelling (AboutKidsHealth, 2017).
+===Exercise or Stretches ===
+Prior to exercising, stretching or massaging tender areas allows for muscles to loosen and minimizes additional stress on affected areas. An important aspect regarding exercise for young children with arthritis is that it is done at a moderate intensity on a regular basis. Building muscle strengthens the support for affected joints, and regular exercise maintains a child’s body mass so that the child does not need to endure additional weight. It is important that children are not over exhausted by physical activity, as this could increase the pain and soreness (AboutKidsHealth, 2017).
+=== Physiotherapy ===
+Physiotherapy assists in reducing stiffness, thus enabling a consistent continuous recovery over a long period of time. In addition to heat and ice physiotherapy, transcutaneous electrical nerve stimulation is a type of physiotherapy that disrupts pain signals from being transmitted to the brain in a non-invasive manner. A small device containing electrodes is attached to the skin on either side of the painful area. Pain relief tends to increase with prolonged use. (AboutKidsHealth, 2017).
+=== Occupational Therapy===
+An occupational therapist assesses, treats and educates individuals and families affected by JIA. Their training focuses on assessing and treating fine motor skills, hand function and the application of hand splints (AboutKidsHealth, 2017).
+===Assistive Devices===
+Assistive devices provide support in completing many of the daily basic tasks. An individual who may have trouble holding a pencil when writing may use an angled writing surface to reduce the stress placed on his/her joints. Something as simple as replacing a notebook with a computer allows the individual to record the notes from class and complete a project at their own pace . A splint is another assistive device that can be customized to adhere with the mold of a child’s hand. This allows for a greater range of motion and reduced contractures, swelling stress and pain. In individuals with knee joint pain, splints can decrease flexion contractures (AboutKidsHealth, 2017).
+==== Drug Therapy ====
+===Nonsteroidal anti-inflammatory drugs (NSAIDs)===
+NSAIDs include common painkillers such as ibuprofen and naproxen. Other commonly used NSAIDs include ketaprofen, diclofenac, and piroxicam (Juvenile Idiopathic Arthritis, 2017). The NSAIDs are not used with the aim of preventing joint damage; they are rather used as a first line of treatment to manage pain and inflammation among children with JIA. NSAIDs work by interfering with prostaglandin synthesis through inhibition of the enzyme cyclooxygenase (COX), thus reducing swelling and pain (Kim, 2010). The most common side effects of NSAIDs are an upset stomach resulting in pain or nausea. However, some less common side effects include dizziness, headaches, bruising or rash (Juvenile Idiopathic Arthritis, 2017).
+===Disease-modifying antirheumatic drugs (DMARDs)===
+<box 45% round right |>{{:graph2345.png|}}</box|Figure 13 shows a graph of the percentage of patients that improved over the study span of six months. Retrieved from (Giannini et al., 1990).>
+DMARDs are usually used as a second option if NSAIDs do not work. They are “slow acting” drugs that can take weeks to six months to work (Brescia, 2016). They act to treat JIA by slowing or stopping the immune system from causing the inflammation that destroys the joints (Juvenile Idiopathic Arthritis, 2017). Since, it is the inflammation is what slowly destroys joint tissue over the years. Some common non-biologic DMARDs include methotrexate, leflunomide, and sulfasalazine (Harris et al., 2014). The most common non-biologic DMARD administered to children with JIA is methotrexate. Methotrexate is a folic acid analogue and it competitively inhibits with dihydrofolate reductase to interfere with purine biosynthesis and DNA production (Harris et al., 2014). Although the mechanism of action for methotrexate is not known, it is suggested that the extracellular adenosine release and its interaction with specific cell surface receptors may be related to the anti-inflammatory effects (Ramanan et al., 2003).
+A study by Giannini et al. 1990 formed the basis for current use of methotrexate in JIA. They conducted a six-month randomized, double blind controlled multicenter study of 127 children with resistant juvenile rheumatoid arthritis. The results indicated that 63% of the group treated with 10 mg/m2, of MTX, improved compared with only 32% of those treated with 5mg/m2, and 36% of the placebo group (Giannini et al., 1990). Figure 13 shows a comparison of the three treatment category outcomes over a period of six months.
+===Biological Response Modifiers===
+Biological medications can be used to treat individuals who are resistant to commonly used antirheumatic drugs. Proinflammatory cytokines involved in the pathogenesis of JIA are the main components of biologic drugs. Etanercept, infliximab, and adalimumab block anti-tumour necrosis factors (TNF-ɑ), thus reducing inflammation. Etanercept is administered through subcutaneous injections, and optimal dosage includes 0.4mg/kg twice a week or 0.8 mg/kg once a week. Infliximab and adalimumab are anti-TNF-α monoclonal antibodies that are administered through IV infusions and subcutaneous injections respectively. A concern with biologic drugs is immunosuppression, thus infections at the site of injection and respiratory tract develop. Furthermore, the reactivation of hepatitis B and tuberculosis are risks that individuals administered with anti-TNF-α agents endure (Ungar, et al., 2013).
+===Corticosteroid Joint Injections===
+In the circumstance that a child does not show significant signs of recovery with the usage of other drug treatments, corticosteroids can be injected into the inflammatory joints. This method is effective as it minimizes the side effects by directly targeting the affected areas. This induces an immediate response within the course of a week. The three corticosteroids that are commonly used include Aristospan, Kenalog and Depo-Medrol. Please refer to Figure 14 to understand the process of injecting corticosteroids into the affected joints (AboutKidsHealth, 2017).
+{{:screen_shot_2017-03-09_at_3.13.23_pm.png|}}
+----
+**Figure 14:**This figure depicts the process of injecting corticosteroids into affected joints in individuals with juvenile idiopathic arthritis. (Retrieved from http://www.aboutkidshealth.ca/En/ResourceCentres/JuvenileIdiopathicArthritis/TreatmentofJIA/MedicationsforJIA/Pages/CorticosteroidJointInjections.aspx)
+==== Surgical Treatment====
+Children must be of at least 6 years of age to be considered for surgery. Even when children are older than 6, surgery is usually very rare because there is a very low risk of a child developing joint damage that’s substantial enough to require some type of surgical intervention. Of the surgical interventions one that seem to be common for children is the soft tissue release of contractures. A contracture is a joint abnormally bent by shortened soft tissues in and around the joint. It involves cutting the excess tissue attached to the abnormally bent joint, and as the tissues are released the joint is able to return more to its normal position (Juvenile Idiopathic Arthritis, 2017). The goal of soft tissue releasing is to (1) return the joint to a closer to normal position, and (2) increase range of motion. After soft tissue release surgery casts are usually worn for several weeks, followed by physiotherapy. Total joint replacement or arthroplasty is another form of surgery and it is practiced as a last resort for damaged joints. Figure 15 shows a patient’s knee after total knee replacement (Abdel & Figgie 2014). Total joint replacement is usually delayed until the child’s bones have stopped growing. This type of surgery can relieve pain and restore joint function but joints will not be restored to normal position. Other surgical methods include osteotomy, epiphysiodesis, synovectomy, and arthrodesis. Osteotomy is when a piece of a bone is removed to allow for better movement. Epiphysiodesis is carried out if there is specifically excessive growth, and the portion that is overgrown is removed. Synovectomy is rarely used in JIA cases, but it is the removal of the synovium to reduce inflammation. Lastly, arthrodesis is also rarely used, as it requires the fusing of two bones in the diseased joint to prevent joint movement.
+{{:bone1.png|}}
+Figure 15. This image shows the view before and after total knee replacement. Retrieved from (Abdel & Figgie, 2014).
+===== Future Directions =====
+The majority of children are treated adequately with a combination of treatments such as NSAIDs, corticosteroids and DMARDs available today. Yet, there are still some children, who are intolerant or resistant to these therapies, hence suffer from joint damage. For children who fall under this category, autologous stem cell transplantation seems to be a potential option (Brinkman et al., 2007). Autologous stem cell transplantation is a procedure where a person’s own stem cells to replace damaged cells (Autologous Transplants,n.d.). This method of treatment has only been tried on a few as thirty children. First, Wulffraat et al., reported positive results of autologous stem cell transplantation in four children (Brinkman et al., 2007).
-====== Conclusion ======
-To summarize, Alzheimer's Disease is a very common case of dementia that has significant implications the future health and well being of elderly patients. Currently, the most accepted hypothesis by scientists is the Beta-amyloid hypothesis which describes possible processing faults involved with the Amyloid Precursor Protein (APP) causing degradation of brain tissue. In most cases, epidemiology shows that age is a main factor for Alzheimer's disease to appear. Characterized by a loss of cognitive function, this debilitating disease unfortunately has no forms of prevention other than eating foods that boost cognitive functions and brain activity. In terms of future research, a novel treatment that has recently been discovered is the use of immunization to stop the development of the disease. Through techniques of active or passive immunization, the administration of antibodies causes alterations and improvement in the beta-amyloid plaques. With such a high onset rate at relatively high ages, future scientific research will be essential to continue to find new preventative measures and more effective treatments.
 ======References======
@@ Line 179: / Line 372: @@
 William C. Shiel Jr., MD, FACP, FACR. (n.d.). Rheumatoid Arthritis (RA) Symptoms & Treatment. Retrieved February 20, 2017, from http://www.onhealth.com/content/1/rheumatoid_arthritis_ra

Differences

Search

Navigation

Print/export

Tools

QR Code